A Randomized Study of Ruxolitinib Tablets Compared to Best Available Therapy in Subjects With Primary Myelofibrosis, Post-Polycythemia Vera-Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 219
- 试验地点
- 1
- 主要终点
- Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 48
研究概览
简要总结
This was an open label, randomized study comparing the efficacy and safety of randomized 2:1 Ruxolitinib tablets versus best-available therapy, as selected by the investigator. The purpose was to compare the efficacy, safety and tolerability of Ruxolitinib (INC424/INCB018424) given twice daily to the best-available therapy, in subjects with primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (PPV-MF) or post essential thrombocythemia myelofibrosis (PET-MF).
详细描述
This study included a randomized treatment phase, followed by an extension phase. The treatment phase lasted from Study Day 1 (day of randomization) to the occurrence of a protocol-specified progressive disease event or study conclusion, whichever came first. The extension phase (including crossover of control group patients) lasted from the progressive disease event until the earliest of the following events: a) the patient was no longer receiving clinical benefit, b) the patient chose to withdraw from the study, or c) the study ended. All patients received ruxolitinib in the extension phase of the study. Maximum individual patient duration was 5 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must be diagnosed with PMF, PPV-MF or PET-MF according to the 2008 World Health Organization criteria
- •Subjects with MF requiring therapy must be classified as high risk OR intermediate risk level 2 according to the prognostic factors defined by the International Working Group
- •Subjects with an ECOG performance status of 0, 1, 2 or 3
- •Subjects with peripheral blood blast count of < 10%.
- •Subjects who have not previously received treatment with a JAK inhibitor
排除标准
- •Subjects with a life expectancy of less than 6 months
- •Subjects with inadequate bone marrow reserve as demonstrated by specific clinical laboratory counts
- •Subjects with any history of platelet counts < 50,000/µL or ANC < 500/µL except during treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for any other reason
- •Subjects with inadequate liver or renal function
- •Subjects with clinically significant bacterial, fungal, parasitic or viral infection which require therapy
- •Subjects with an active malignancy over the previous 5 years except specific skin cancers
- •Subjects with severe cardiac conditions
- •Subjects who have had splenic irradiation within 12 months
研究组 & 干预措施
Ruxolitinib
5 mg tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
干预措施: Ruxolitinib (Drug)
Best Available Therapy (BAT)
Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
Patients randomized to BAT were eligible to cross over to receive open-label ruxolitinib after a qualifying progression event, if they met the safety criteria. After the primary analysis in January 2011, patients randomized to receive BAT were allowed to cross over to receive ruxolitinib and move to the extension phase of the study without a qualifying progression event.
干预措施: Best Available Therapy (BAT) (Drug)
结局指标
主要结局
Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 48
时间窗: Baseline, Week 48
The change in spleen volume from baseline to week 48 was measured by magnetic resonance imaging (MRI) (or by computer tomography (CT) for participants unable to undergo MRI) and was calculated only for participants who had an evaluable spleen volume at baseline. The percentage of participants achieving a greater than or equal to 35% reduction in spleen volume from baseline to week 48 was then calculated by treatment group.
次要结局
- Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates)(Baseline, up to Year 5)
- Leukemia-free Survival (LFS)(Time from randomization and earliest of either leukemia or death)
- Percentage of Participants With Bone Marrow Histomorphology at Week 48 (Primary Analysis)(48 weeks)
- Progression-free Survival (PFS)(Time from randomization and the earliest of either increase in spleen volume >=25% from on-study nadir, splenic irradiation, splenectomy, leukemic transformation or death)
- Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24(Baseline, Week 24)
- Time to First at Least 35% Reduction in Spleen Volume From Baseline by Treatment (Primary Analysis)(Time from randomization and date of the first MRI showing at least 35% reduction from baseline in spleen volume)
- Duration of Maintenance of Spleen Volume Reduction (Median)(Baseline, up to Year 5)
- Bone Marrow Histomorphology(Baseline, once a year)
- Overall Survival (OS)(From randomization until death from any cause)
- Duration of Follow-up by Treatment(baseline, 260 weeks (end of study))